Browsing by Subject "Short chain fatty acids"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women
    (Nature Research, 2018-11-20) Dugas, Lara R.; Bernabé, Beatriz Peñalver; Priyadarshini, Medha; Fei, Na; Park, Seo Jin; Brown, Laquita; Plange-Rhule, Jacob; Nelson, David; Toh, Evelyn C.; Gao, Xiang; Dong, Qunfeng; Sun, Jun; Kliethermes, Stephanie; Gottel, Neil; Luke, Amy; Gilbert, Jack A.; Layden, Brian T.; Microbiology and Immunology, School of Medicine
    We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m2) and 50% obese (BMI ≥ 30 kg/m2)] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.
  • Thumbnail Image
    Item
    Fructooligosaccharides act on the gut-bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice
    (Oxford University Press, 2024-02-21) Islam, Proapa; Ice, John A.; Alake, Sanmi E.; Adedigba, Pelumi; Hatter, Bethany; Robinson, Kara; Clarke, Stephen L.; Ford Versypt, Ashlee N.; Ritchey, Jerry; Lucas, Edralin A.; Smith, Brenda J.; Obstetrics and Gynecology, School of Medicine
    Targeting the gut-bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (P < .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, Sost, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.
  • Thumbnail Image
    Item
    Microbiota, metabolic profiles and immune biomarkers in infants receiving formula with added bovine milk fat globule membrane: a randomized, controlled trial
    (Frontiers Media, 2024-10-04) Christensen, Chloe; Kok, Car Reen; Harris, Cheryl L.; Moore, Nancy; Wampler, Jennifer L.; Zhuang, Weihong; Wu, Steven S.; Hutkins, Robert; Izard, Jacques; Auchtung, Jennifer M.; Pediatrics, School of Medicine
    Introduction: Few studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition. Methods: In this double-blind randomized study, infants (7-18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother's own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites. Results: At Day 60, stool bacterial diversity and richness were higher in formula groups vs HM, as were Bifidobacterium bifidum and B. catenulatum abundance. Compared to HM, stool pH was higher in Control, while acetate, propionate, isovalerate, and total short- and branched-chain fatty acids were higher in INV-MFGM. Butyrate and lactate increased for INV-MFGM from baseline to Day 60. No group differences in oral microbiota or immune markers (α- and β-defensin, calprotectin, or sIgA) were detected, although sIgA increased over time in all study groups. Added bovine MFGM in infant formula modulated stool microbiota and short- and branched-chain fatty acids compared to human milk; changes were modest relative to control formula. Discussion: Overall, distinct patterns of stool metabolites and microbiota development were observed based on early nutrition.
  • Thumbnail Image
    Item
    Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC
    (BMJ, 2023) Awoniyi, Muyiwa; Wang, Jeremy; Ngo, Billy; Meadows, Vik; Tam, Jason; Viswanathan, Amba; Lai, Yunjia; Montgomery, Stephanie; Farmer, Morgan; Kummen, Martin; Thingholm, Louise; Schramm, Christoph; Bang, Corinna; Franke, Andre; Lu, Kun; Zhou, Huiping; Bajaj, Jasmohan S.; Hylemon, Phillip B.; Ting, Jenny; Popov, Yury V.; Hov, Johannes Roksund; Francis, Heather L.; Sartor, Ryan Balfour; Medicine, School of Medicine
    Objective: Conflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models. Goal: define the function of complex resident microbes and their association relevant to PSC patients by studying germ-free (GF) and antibiotic-treated specific pathogen-free (SPF) multidrug-resistant 2 deficient (mdr2-/- ) mice and microbial profiles in PSC patient cohorts. Design: We measured weights, liver enzymes, RNA expression, histological, immunohistochemical and fibrotic biochemical parameters, faecal 16S rRNA gene profiling and metabolomic endpoints in gnotobiotic and antibiotic-treated SPF mdr2-/- mice and targeted metagenomic analysis in PSC patients. Results: GF mdr2-/- mice had 100% mortality by 8 weeks with increasing hepatic bile acid (BA) accumulation and cholestasis. Early SPF autologous stool transplantation rescued liver-related mortality. Inhibition of ileal BA transport attenuated antibiotic-accelerated liver disease and decreased total serum and hepatic BAs. Depletion of vancomycin-sensitive microbiota exaggerated hepatobiliary disease. Vancomycin selectively decreased Lachnospiraceae and short-chain fatty acids (SCFAs) but expanded Enterococcus and Enterobacteriaceae. Antibiotics increased Enterococcus faecalis and Escherichia coli liver translocation. Colonisation of GF mdr2-/- mice with translocated E. faecalis and E. coli strains accelerated hepatobiliary inflammation and mortality. Lachnospiraceae colonisation of antibiotic pretreated mdr2-/- mice reduced liver fibrosis, inflammation and translocation of pathobionts, and SCFA-producing Lachnospiraceae and purified SCFA decreased fibrosis. Faecal Lachnospiraceae negatively associated, and E. faecalis/ Enterobacteriaceae positively associated, with PSC patients' clinical severity by Mayo risk scores. Conclusions: We identified novel functionally protective and detrimental resident bacterial species in mdr2-/- mice and PSC patients with associated clinical risk score. These insights may guide personalised targeted therapeutic interventions in PSC patients.